Lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, has been shown to have a strong adjuvant effect towards inhaled antigens contributing to airway inflammation. Isoflavones are anti-inflammatory molecules present in abundant quantities in soybeans. We investigated the effect of isoflavones on human dendritic cell (DC) activation via LPS stimulation and subsequent DC-mediated effector cell function both in vitro and in a mouse model of upper airway inflammation. Human monocyte-derived DCs (MDDC) were matured with LPS (or TNF-α) +/− isoflavones (genistein or daidzein). The surface expression levels of DC activation markers were analyzed by flow cytometry. Mature DCs +/− isoflavones were washed and cultured with freshly-isolated allogenic naïve CD4+ T cells for 5 days or with autologous natural killer (NK) cells for 2 hours. The percentages of proliferating IFN-γ+ CD4+ T cells and cytokine levels in culture supernatants were assessed. NK cell degranulation and DC cytotoxicity were measured by flow cytometry. Isoflavones significantly suppressed the activation-induced expression of DC maturation markers (CD83, CD80, CD86) and MHC class I but not MHC class II molecules in vitro. Isoflavone treatment inhibited the ability of LPS-DCs to induce IFN-γ in CD4+ T cells. NK cell degranulation and the percentage of dead DCs were significantly increased in isoflavone-treated DC-NK co-culture experiments. Dietary isoflavones suppressed the mucosal immune response to intra-nasal sensitization of mice to ovalbumin. Similar results were obtained when isoflavones were co-administered during sensitization. These results demonstrate that soybean isoflavones suppress immune sensitization by suppressing DC-maturation and its subsequent DC-mediated effector cell functions.

We demonstrate that peanut agglutinin, a minor peanut allergen, is a novel ligand for DC-SIGN. Peanut agglutinin activates DCs to induce the expression of costimulatory molecules in vitro. We present a comprehensive report on the characterization of DC-SIGN-binding proteins in common allergenic foods such as peanut, soy, tree nuts, egg, and milk. Foods that rarely induce allergy, such as pine nuts, chickpea, and corn, showed no binding to DC-SIGN. Several DC-SIGN-binding proteins show reactivity in serum IgE immunoblots. We have also identified novel non-IgE-binding proteins that interact with DC-SIGN; these proteins may be important for regulating immune responses to these foods.

Background: Food allergy research is hampered by a lack of animal models that consistently mimic human food allergic responses. Laboratory mice are generally fed grain-based chow made with large amounts of soybeans rich in immunomodulatory isoflavones. We tested the role of dietary soy components in the induction of food allergic responses in the BALB/c mouse strain, which is known to be resistant to anaphylaxis when orally challenged by food allergens. Methods: Mice were fed a soy-free diet for 2 generations. After weaning, mice were maintained on the same diet or fed a diet containing soy isoflavones, i.e. genistein and daidzein, followed by weekly oral sensitizations with crude peanut extract plus cholera toxin and finally challenged at week 7. The anaphylactic symptoms, body temperature, peanut-specific antibodies and mast cell degranulation were assessed. Results: Soy-free diet mice showed significantly higher anaphylactic symptom scores and mast cell degranulation after challenge and higher peanut-specific antibody levels than mice fed regular chow. Introduction of a regular soy diet or an isoflavone diet to soy-free diet mice significantly suppressed the allergic reactions compared to the soy-free diet. Conclusion: Rodent diet is an important variable and needs to be taken into consideration when designing experiments involving animal models. Our results indicate that elimination of soy components from the diet enhances peanut sensitization in BALB/c mice. In addition to serving as a valuable tool to mimic human food allergy, the dietary influence on the immune response could have far-reaching consequences in research involving animal models.

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